Our final study investigated the mechanism(s) by which IGF-I up-regulates LPH activity. The three treatment groups were: 100% TPN, 20% PEN with or without 1.0 mg/kg IGF-I. IGF-I increased LPH activity and LPH activity per unit mature LPH ∼2-fold over PEN alone, but did not affect LPH mRNA or the relative abundance of proLPHh or mature LPH. Fractional and absolute synthesis rates of mucosal protein and LPH were similar among the treatment groups. Total mucosal protein synthesis was increased 60% in the IGF-I treated animals. Based on these data, we speculate that the mechanism by which IGF-I up-regulates LPH is post-translational, either via reducing LPH degradation or specifically altering LPH enzyme kinetics.